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Hypothyroidism and
Hyperthyroidism
Diagnosis and Management
Learning Objectives
 Recognize the signs and symptoms,
risk factors, screening and diagnosis,
and management of hypothyroidism
and hyperthyroidism.
Outline
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Introduction
Anatomy and Physiology
Hypothyroidism
Hyperthyroidism
Risk Factors, Screening, and
Diagnosis
 Management
Introduction
 Thyroid disorders common in primary
care practice
 Thyroid disease affects approximately
5% of adults in the U.S.
 Insidious onset
 May be confused with other common
medical conditions
Introduction
 Several thyroid disorders exist:
• Hyperthyroidism
• Hypothyroidism
• Thyroid cysts
• Goiter
• Malignancies
 Hypothyroidism and hyperthyroidism
will be discussed
Anatomy and Physiology
 Thyroid located in anterior neck
 Gland composed of 2 lobes
connected by an isthmus
 Gland composed of follicular
cells, lymphoid cells, “C” cells,
colloid, interstitial tissue
 Two primary hormones: T4 and T3
Thyroid Hormones
 T4 produced in greater quantities
than T3
 Approximately 50% of T4 converted
to T3 by deiodination at peripheral
tissue cells
Thyroid Hormones
 Approximately 70-90% of circulating T3
is derived by deiodination of T4
 Approximately 99.9% of T4 and T3
secreted from thyroid attached to
carrier proteins
Thyroid Hormones
 TSH from anterior pituitary stimulates
thyroid gland to produce and secrete
T4 and T3
 TRH from hypothalamus stimulates
pituitary gland to produce and release
TSH
Hypothyroidism
Hashimoto’s thyroiditis
Postpartum thyroiditis
Subacute/DeQuervain thyroiditis
Riedel’s thyroiditis
Hypothyroidism in infancy and
childhood
 Myxedema coma
 Subclinical hypothyroidism
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Hypothyroidism
 Most common thyroid disorder
• Affects 1-2% of U.S. population
 Women affected 14x more
often than men
Hypothyroidism
 Most common cause
worldwide: dietary iodine deficiency
 Most common cause in U.S.:
autoimmune thyroiditis (Hashimoto’s
Thyroiditis)
Hypothyroidism
 Deficiency in production and secretion
of T4 and T3
 Primary hypothyroidism:
• Increased serum TSH
 Secondary hypothyroidism
• Low serum TSH
 Also known as myxedema
Hypothyroidism
 Asymptomatic/mild presentations very
common
 Signs and symptoms:
• Fatigue
• Cold intolerance
• Weight changes
• Weakness
• Hoarseness
Hypothyroidism
 Signs and symptoms:
• Dry skin
• Brittle nails and hair
• Bradycardia
• Depression
• Lethargy
• Constipation
• Menstrual abnormalities
Hypothyroidism
 Signs and symptoms:
• Anemia
• Hyponatremia
• Galactorrhea
• Goiter
• Hard, pitting edema of lower
extremities
• Delayed return of deep tendon
reflexes
Hypothyroidism
 Weight gain usual
• Obesity rarely associated with
hypothyroidism
 Multiple organ systems affected
• Overproduction of keratin in skin
• GI tract dysfunction
• Cardiac dysfunction
• Anemia common (25-50% of patients)
Hypothyroidism
 Endocrine system effects:
• Galactorrhea caused by increased
prolactin secretion
• Decreased GH secretion and action
• Schmidt syndrome
• Primary adrenocortical
insufficiency
Hashimoto’s Thyroiditis
 Chronic lymphocytic thyroiditis
 Chronic autoimmune thyroiditis
 Caused by:
• Antithyroid peroxidase antibodies
• Antithyroglobulin antibodies
 Antibodies cause thyroid
injury
 Overt hypothyroidism, rare initial
hyperthyroidism
Postpartum Thyroiditis
 Usually presents as overt
hypothyroidism
 May have associated goiter
 Occurs within first 6 postpartum
months
 Non-tender gland
 Self-limiting
 No treatment required usually
Subacute Thyroiditis
 May be associated with a viral infection
 Gland usually tender
 Fever, sore throat, malaise may be
present
 Elevated ESR
 Self-limiting
 Lasts 1-3 months
 NSAIDs for pain, fever prn
Riedel’s Thyroiditis
 Rare
 Middle-aged or elderly women
 Enlarged, asymmetric, stony hard
gland adherent to neck structures
 Local pain, dysphagia, dyspnea,
hoarseness
 Treated with Tamoxifen [generic]
Hypothyroidism in Infancy and
Childhood
 Infancy – cretinism
• Puffy hands/face, mental retardation
• Deafness, growth failure
 Childhood hypothyroidism
• Retarded bone development
• Decrease in longitudinal growth
• Slowed mentation
• Delayed sexual maturation
Myxedema Coma
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Medical emergency
High mortality rate
Rare
Occurs in older women as a
consequence of poorly controlled or
untreated hypothyroidism
 Hospitalization, sepsis, exposure to
cold, trauma
Myxedema Coma
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Altered consciousness, coma
Hypothermia
Bradycardia
Hypotension
Reduced ventilatory rate
Hypoglycemia, hyponatremia,
elevated TSH
Myxedema Coma
 Treatment:
• Intubation and mechanical
ventilation
• Control hypothermia
• Volume expansion
• Large dose of Levothyroxine
(synthetic T4) [generic], then daily
therapy
Subclinical Hypothyroidism
 Usually asymptomatic
 TSH concentration 5-20 mU/L (normal
0.5-5.0 mU/L)
 Normal T4 concentration
Hyperthyroidism
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Apathetic hyperthyroidism
Graves’s Disease
Subclinical hyperthyroidism
Thyroid Storm
Hyperthyroidism
 Excess T4 and T3 production from
thyroid
 Thyrotoxicosis:
• Excess serum concentration of T4
and/or T3 from any source
 Signs and symptoms:
• Heat intolerance
• Weight loss
• Sweating
Hyperthyroidism
 Signs and symptoms:
• Anxiety
• Loose stools
• Fatigue
• Weakness
• Menstrual irregularity
• Tachycardia
Hyperthyroidism
 Signs and symptoms:
• Hypertension
• Warm, moist skin
• Palpitations
• Tremor
• Insomnia
• Goiter (Graves’)
• Ophthalmopathy (Graves’)
Hyperthyroidism
 Cardiac effects of excess thyroid
hormone:
• More likely in older individuals
• Ischemic CHF with preexisting
CAD
• Atrial fibrillation
• May be only clinical
sign in older persons
Apathetic Hyperthyroidism
 Uncommon
 Should consider dx in elderly
individuals who exhibit persistent signs
of depression and/or dementia
 Should consider dx in older individuals
with recent, significant mood change
 Apathy, weight loss, lethargy, very low
serum TSH concentration
Hyperthyroidism
 Affects women > men
 Graves’ Disease most common
condition
• 60-90% of all cases of
hyperthyroidism
Hyperthyroidism
 Affects women > men
 Graves’ disease most common
condition
• 60-90% of all cases of
hyperthyroidism
 Postpartum thyroiditis (transient)
 Toxic multinodular goiter
 Thyroid adenoma
 Excess exogenous thyroid hormone
Graves’ Disease
 Autoimmune disorder:
• Presence of TSH receptor-stimulator
antibodies (TSH RS Abs)
• Antibodies act on follicular cells
causing release of excess quantities
of T4 and T3
 Laboratory: elevated T4 and T3, low
concentration of TSH
Graves’ Disease
 Stimulus for TSH RS Abs:
• Environmental factors
• Pregnancy
• Viral exposure
 Occurs more often in:
• Women than men (8:1)
• 30-60 year olds
Graves’ Disease
 Occurs more often in:
• Individuals with other
autoimmune diseases (type 1
diabetes)
• Smokers
• Family history of autoimmune
thyroid disease
• History of neck irradiation
Graves’ Disease
 Thyrotoxic signs and symptoms
caused by excess hormone
 Excess hormone does not cause goiter,
ophthalmopathy, or local
myxedematous skin changes
 Goiter occurs in almost all patients
• Caused by thyroid gland
overstimulation
Graves’ Ophthalmopathy
 Exophthalmos:
• Retrobulbar connective tissue
hypertrophy
• Fibrous enlargement of extraocular
muscles
 Lid lag/proptosis may cause corneal
drying or keratosis leading to blindness
 Clinically evident in 10-25% of patients
Graves’ Disease
 Myxedematous skin changes:
• Thickening
• Pretibial areas
• Treatment: application of topical
glucocorticoids
Subclinical Hyperthyroidism
 Asymptomatic
 Serum TSH concentration < 0.5 mU/L
(normal 0.5-5.0 mU/L)
 Normal levels of T4 and T3
Thyroid Storm
 Extreme form of thyrotoxicosis
 Uncommon
 Usually associated with
preexisting thyrotoxicosis
• Graves’ Disease
• Toxic multinodular goiter
 Abrupt onset
Thyroid Storm
 Precipitated by trauma, infection,
surgery
 Thyroid hormone levels elevated same
as other patients with thyrotoxicosis
 Hypermetabolic state:
• Profuse sweating
• Fever
• Tachycardia
• Tremulousness
Thyroid Storm
 CHF and pulmonary edema secondary
to cardiac arrhythmias
 Nausea/vomiting/abdominal pain
 Delerium and psychosis common, then
apathy, stupor, coma
 Exophthalmos and/or goiter
 ICU admission
Thyroid Storm
 Treat fever and dehydration
 Treat precipitating cause, if known
 Beta-blocker therapy for tachycardia,
tremor, sweating
 Treat hypernatremia if present
 Treatment goal: disrupt adrenergicallymediated thyroid hormone action and
inhibit further hormone synthesis and
release
Thyroid Storm
 Propylthiouracil (PTU) [generic]:
• Antithyroid agent
• Inhibits synthesis of thyroid hormone
from gland
• Inhibits synthesis of more T3 from
T4 at peripheral tissues
• Given orally, via NG tube, or rectally
Thyroid Storm
 Saturated solution of potassium iodide
(SSKI) or sodium iodide:
• Given after first dose of PTU
• Don’t postpone use if PTU not
available
• Inhibits synthesis of hormones from
thyroid gland
Thyroid Storm
 Dexamethasone [generic]:
• Inhibits further hormone release
from gland
• Inhibits peripheral synthesis of T3
from T4
• Synergistic effect with PTU and
iodine
• Brings serum T3 concentration to
normal limits within 24-48 hours
Risk Factors, Screening, and
Diagnosis
 Thyroid dysfunction may progress
slowly
 Signs and symptoms may not be
readily recognized
 Many individuals have undiagnosed
disease
Risk Factors, Screening, and
Diagnosis
 All adults > 35 years old should be
screened every 5 years
 All newborns undergo federally
mandated screening
 More frequent screening is
recommended for individuals
at higher risk
Risk Factors for Thyroid Disease
 Strong family history of thyroid disease
 Women 4-8 weeks postpartum
 Presence of other autoimmune disease
(type 1 diabetes)
 Postmenopausal women, elderly
 Laboratory evidence of
hypercholesterolemia, elevated LFTs,
elevated CPK and LDH
Risk Factors for Thyroid Disease
 Presence of anemia
 Presence of hyponatremia,
hypercalcemia
 Presence of hyperprolactinemia
Laboratory Screening
 TSH most reliable screening test
• Inexpensive, fast, accurate, safe
 Normal TSH: 0.5-5.0 mU/L
• Assay of T4 or T3 not required if
TSH normal
Laboratory Diagnosis
 Serum TSH
 Serum free T4 (FT4)
• Physiologically active
• More sensitive
 Serum T3/serum free T3 (FT3)
 Thyroid carrier proteins:
• Thyroglobulin
• Thyroid binding globulin
Laboratory Diagnosis
 Antithyroid antibodies:
• Antithyroglobulin abs
• Antithyroid peroxidase abs
• TSH receptor-blocker abs
• TSH receptor-stimulator abs
Laboratory Diagnosis of
Hypothyroidism
 TSH is usually increased
• Overt hypothyroidism: > 20 mU/L
• Subclinical hypothyroidism: 5-20
mU/L
 T4:
• Subclinical hypothyroidism: normal
• Overt hypothyroidism: low
 T3 assay not recommended to
diagnose hypothyroidism
Laboratory Diagnosis of
Hypothyroidism
 Hashimoto’s Thyroiditis:
• Elevated antithyroid peroxidase
abs
• Elevated antithyroglobulin abs
Laboratory Diagnosis of
Hyperthyroidism
 TSH usually < 0.1 mU/L in primary
hyperthyroidism
• Serum FT4 should also be assayed
• If normal, serum T3 assay should
be performed
• Serum T3 will be increased in
primary hyperthyroidism when FT4
is normal
Laboratory Diagnosis of
Hyperthyroidism
 Subclinical hyperthyroidism:
• Serum TSH concentration < 0.5 mU/L
• Normal serum T4 and T3
 Graves’ Disease:
• Positive TSH RS abs
Imaging Studies in Thyroid
Disease
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Ultrasound
Scintigraphy
MRI
CT
Ultrasound and scintigraphy most
commonly used
Ultrasound
 Discerns structure of thyroid masses
 Nodules, adenomas, simple and
complex cysts can be identified
 Used for localization of a mass for fine
needle aspiration (FNA)
 Assess gland size
Radioactive Scintigraphy
 Evaluates thyroid anatomy and
function
 123[I] and Technetium-99m (99m[Tc]) used
for diagnostic thyroid scan
 131[I] scintigraphy utilized in total body
scanning for presence of metastatic
thyroid cancer
Radioactive Scintigraphy
 2 Phases:
• Thyroid scan to assess anatomy
at 2-6 hours
• Thyroid uptake to assess function
at 24 hours
 Assesses functional status of
adenomas and nodules
 Assesses gland hyper- or hypofunction
Radioactive Scintigraphy
 Useful in evaluating patients with
thyrotoxic signs and symptoms
• Marked decrease in thyroid gland
activity in thyroiditis
• Hyperfunctioning gland in Graves’
Disease
• Hypofunctioning gland in factitious
thyrotoxicosis
Radioactive Scintigraphy
 Absolutely contraindicated in pregnant
women
 Relatively contraindicated in nursing
women
 99m[Tc] should be used in patients with
iodine allergy
Fine Needle Aspiration
 FNA:
• Biopsy palpable nodules,
drain simple cysts
Surgery
 Surgery:
• Goiters impinging on neck structures
• Pregnant patients with Graves’
Disease not controlled with
antithyroid drugs
• Suspected or diagnosed thyroid
cancer
Management of Hypothyroidism
 Synthetic T4 (Levothyroxine [generic],
Synthroid [brand]):
• Mainstay of therapy for many years
• Partially converted to T3 in periphery
• Starting dose 50-100 mcg/day
• Starting dose 25-50 mcg/day:
• Patients with CAD
• Patients > 60 years old
Management of Hypothyroidism
 Synthetic T4 (Levothyroxine [generic],
Synthroid [brand]):
• Usual maintenance dose 100-250
mcg/day
• TSH assay 6 weeks after initiating or
changing therapy
• Keep TSH in normal range (0.5-5.0
mU/L)
Management of Hypothyroidism
 Desiccated thyroid (T4 and T3)
used successfully in past
 Some endocrinologists now
prescribe synthetic T3
(Liothyronine [generic], Cytomel®)
in addition to Levothyroxine
Management of Hypothyroidism
 Starting dose of Liothyronine is
12.5 mcg/day in place of 50 mcg
of Levothyroxine
 Keep TSH in normal range
Management of Hypothyroidism
 Some patients require life-long
thyroid hormone replacement
therapy
 Thyroid hormone overreplacement should be avoided:
• Cardiac stimulant
• Increases bone turnover and is
an etiology of secondary
osteoporosis
Management of Subclinical
Hypothyroidism
 Recommend a trial of therapy in subset
of patients:
• Symptomatic
• Elevated LDL-C
• TSH concentration > 10 mU/L on at
least 2 assays at least 1 month apart
 Assay TSH 6 weeks after
initiating/changing therapy
Management of Subclinical
Hypothyroidism
 Maintain TSH in normal range
 In patients not receiving
Levothyroxine therapy:
• Check TSH every 3-6 months or
when symptoms occur
Management of Hyperthyroidism
 Patients should be referred to an
endocrinologist for definitive
treatment
 Pharmacological agents initially
 Radioactive iodine ablation of
thyroid
 Subtotal thyroidectomy
Antithyroid Drug Therapy
 Acute hyperthyroid symptoms
 Goal of therapy:
• Inhibit peripheral conversion of T4 to
T3
• Inhibit synthesis and release of T4
and T3 from thyroid gland
 Propylthiouracil (PTU)
 Methimazole [generic] or Tapazole®
Antithyroid Drug Therapy
 PTU:
• Inhibits peripheral conversion of T4
to T3
• Inhibits thyroid hormone synthesis
and release from thyroid gland
 Methimazole [generic]:
• Inhibits thyroid hormone synthesis
and release from thyroid gland
Antithyroid Drug Therapy
 May be used as primary therapy
• Not to exceed 24 months:
hypothyroidism
 May be used as adjunctive therapy
 PTU dosage: 50-100 mg PO q8h
 Methimazole dosage: 10-20 mg q8h or
60 mg as single daily dose
Antithyroid Drug Therapy
 Skin rashes in approximately 3-5% of
patients
 0.5% develop granulocytopenia
 Myalgias, arthralgias
 Rarely aplastic anemia
 Evaluate patient every 3-4 months
 Perform TSH every 3 months x 1 yr,
then every 6 months x 1 yr, then
annually after treatment stopped
Management of Hyperthyroidism
 Beta-blocker therapy:
• Ameliorates tachycardia, sweating,
tremor, nervousness
• Propanolol: starting dose 20-40 mg
PO q6h
• Caution in patients with CHF or
bronchospasm
Radioactive Iodine 131[I] Ablation
 Treatment of choice in patients > 21
years old with Graves’ Disease
 Treatment of choice in patients < 21
years old without remission after
antithyroid drug therapy
 Treatment of choice in patients with
toxic multinodular goiter or toxic
thyroid adenoma
Radioactive Iodine Ablation
 Single dose of 131[I] orally
 80% euthyroid after single dose
 > 50% of patients will develop
hypothyroidism
• Assay TSH every 3 months after
therapy
Radioactive Iodine Ablation
 Levothyroxine therapy when patient
becomes hypothyroid
 Life-long Levothyroxine therapy
 RIA contraindicated in pregnancy,
lactation, iodine allergy
• Screen pre-menopausal women for
pregnancy prior to treatment
Subtotal Thyroidectomy
 Pregnant patients who cannot be
managed on antithyroid drugs or
who have side effects
 Patients who refuse radioactive iodine
ablation whose symptoms are not
improved with antithyroid drugs
 Patients with obstructive goiters
Subtotal Thyroidectomy
 Surgical complications:
• Vocal cord paralysis (1%)
• Hypothyroidism (up to 43% after 10
years)
• Hypoparathyroidism
• Recurrence of hyperthyroidism (1015%)
Management of Subclinical
Hyperthyroidism
 Radioactive iodine uptake and scan
recommended for those patients who
are candidates for antithyroid drug
therapy or radioactive ablation
• Hyperthyroid symptoms
• Atrial fibrillation
• Supraventricular tachycardia
• Postmenopausal with decreased
bone density
Summary
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Introduction
Anatomy and Physiology
Hypothyroidism
Hyperthyroidism
Risk Factors, Screening, and Diagnosis
Management
References
 Tierney, Lawrence M., McPhee, Stephen
J., Papadakis, Maxine A. (Eds.). (2004).
Current medical diagnosis and
treatment (43rd ed.). New York:
McGraw-Hill.
 Wilson, George R. (2002). Thyroid
disorders [Electronic version]. Clinics
in Family Practice, 4, 667-771.
References
 Ladenson, Paul W., M.D., et al. (2000).
American Thyroid Association
Guidelines for Detection of Thyroid
Dysfunction [Electronic version].
Archives of Internal Medicine, 160,
1573-1575.
 Evans, Timothy C., M.D. (2003). Thyroid
disease [Electronic version]. Primary
Care: Clinics in Office Practice, 4, 625640.
References
 Surks, Martin I., MD. (1990). American
Thyroid Association Guidelines for Use
of Laboratory Tests in Thyroid Disorders
[Electronic version]. Journal of the
American Medical Association, 263,
1529-1532.
 Davies, Terry F. and Larsen, P. Reed.
Thyrotoxicosis [Electronic version]. In:
Williams Textbook of Endocrinology. St.
Louis: W.B. Saunders, 2003: 413.
References
 Ferri, Fred F. Hyperthyroidism
[Electronic version]. In: Ferri’s Clinical
Advisor: Instant Diagnosis and
Treatment. St. Louis: Mosby, 2004, 460461.